The susceptibility of the developing nervous system to environmental agents has been a major concern with regard to children's health issues. While current exposure levels to environmental agents does not represent an acute injury, disruption to the nervous system may be associated with either a structural alteration in the formation of the neural network and/or in nervous system functioning. The formation and interactions between the various cell types in the brain are critically timed events.Such windows of vulnerability is assummed to be a major component in the differential susceptibility of the developing organism to environmental insult. This project examines chemical induced perturbations during development of the nervous system as indicated by various alterations in the morphology and molecular profile in the developing brain and associated neurobehavioral outcome of such exposure. The specific projects under study include 1) Neurobehavioral effects of thimerosal in immature SJL autoimmune mice, replication and expansion of literature report. 2) Establishment of a mouse model to examine the neurodevelopmental toxicities of environmental chemicals that perturb thyroid hormone homeostatic maintenance during gestational and postnatal development - we have confirmed alterations in the morphology of Golgi stained neurons in the hippocampus and cerebellum with 3 such chemicals. 3) Inorganic lead is a known developmental neurotoxicant - the ontogenic profile via cDNA array suggests target genes in the mouse associated with early maturation of the blood brain barrier and chloroid plexus 4) specific alterations are being examined in the aged non-human primate brain as a result of early developmental lead exposure. For these studies we continue to use a number of methods to examine alterations in the developing nervous system following exposure to environmental agents including immunohistochemistry, molecular techniques to examine mRNA levels, as well as assessment of neurobehavioral functioning.